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RF-Carvedilol and Its Applications in Dermatology
FR-Carvedilol y sus aplicaciones en dermatología
J.M. Llamas-Molina
, Á. Ayén-Rodríguez, F.J. De la Torre-Gomar
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Servicio de Dermatología, Hospital Universitario San Cecilio, Granada, Spain
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De la Torre-Gomar" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J.M." "apellidos" => "Llamas-Molina" "email" => array:1 [ 0 => "josellamas94@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Á." "apellidos" => "Ayén-Rodríguez" ] 2 => array:2 [ "nombre" => "F.J." "apellidos" => "De la Torre-Gomar" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Universitario San Cecilio, Granada, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "FR-Carvedilol y sus aplicaciones en dermatología" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Carvedilol is a nonselective β-blocker indicated for the treatment of essential hypertension, ischemic heart disease, and heart failure. In dermatology, it has proven useful as an off-label treatment for several skin conditions (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The most common adverse effects reported for standard doses are hypotension, dizziness, nausea, and weakness. These are typically mild and do not generally require dose adjustments or treatment discontinuation.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Flushing and Rosacea</span><p id="par0010" class="elsevierStylePara elsevierViewall">In recent years, carvedilol has been proposed as a promising option for the treatment of flushing and persistent facial erythema in patients with rosacea who do not respond to conventional treatment. The mechanism of action seems to be related to blockade of the β2 adrenergic receptor, which induces vasoconstriction in the dermal plexus. It also decreases heart rate, which may further help improve facial redness.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Mouse models have shown that carvedilol can reduce inflammatory reactions and erythema by inhibiting the TLR2 pathway in macrophages.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The most common dosage for rosacea is 6.25 to 12.5<span class="elsevierStyleHsp" style=""></span>mg 2 or 3 times a day. Improvements are usually observed within 2 to 3 weeks of treatment initiation and tend to last.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Red Scrotum</span><p id="par0020" class="elsevierStylePara elsevierViewall">Red scrotum syndrome is characterized by persistent erythema of the scrotum associated with hyperalgesia and a burning sensation. It is a diagnosis of exclusion. None of the treatments used to date have shown consistent results, and patients who do respond usually need between 4 and 18 months for their symptoms to resolve. The literature contains cases reports of 2 patients with red scrotum who achieved a complete response to once-daily carvedilol 6.25<span class="elsevierStyleHsp" style=""></span>mg after just 4 weeks of treatment. Neither of the patients developed adverse effects nor experienced recurrence after 6 months of treatment.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Red Vulva</span><p id="par0025" class="elsevierStylePara elsevierViewall">Red vulva syndrome is a chronic condition of unknown etiology. It is characterized by persistent redness of the vulva, usually accompanied by pruritus and hyperalgesia. Similarly to in red scrotum syndrome, diagnosis is by exclusion.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Topical corticosteroids cannot be used continuously to treat red vulva syndrome, and, to date, no effective treatments have been identified. The literature contains 2 case reports of red vulva syndrome treated with carvedilol. Both patients showed a marked, rapid response (after 3 and 4 weeks of treatment) to carvedilol 6.25<span class="elsevierStyleHsp" style=""></span>mg applied once daily 3 days a week; no adverse effects were reported.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prevention of Carcinogenesis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Carvedilol has shown skin cancer preventive effects both in vivo and in vitro. Its inhibitory effect on carcinogenesis appears to be multifactorial. It protects against UV radiation–induced damage by regulating DNA repair mechanisms and also blocks reactive oxygen species and certain oncogenic signaling pathways such as PI3K/AKT. New topical preparations are being developed to avoid adverse effects caused by systemic absorption.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1716016" "titulo" => "Keywords" ] 1 => array:2 [ "identificador" => "xpalclavsec1716017" "titulo" => "Palabras clave" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Flushing and Rosacea" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Red Scrotum" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Red Vulva" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Prevention of Carcinogenesis" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of Interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1716016" "palabras" => array:5 [ 0 => "Carvedilol" 1 => "Flushing" 2 => "Facial erythema" 3 => "Red scrotum syndrome" 4 => "Non-melanoma skin cancer" ] ] ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: bid, twice a day; CR, complete response; F, female; M, male; PR, partial response; tid, 3 times a day.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Skin condition \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Publication \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study design \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Carvedilol dosage \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Concomitant treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Response \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adverse effects \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Follow-up \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Red vulva \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hajj et al. (2018) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case series (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2)F 40 yF 60 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.25<span class="elsevierStyleHsp" style=""></span>mg/d 3 days a week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">F 40 y, CR (4 wk)F 60 y, PR (3 wk) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M 40 y, no recurrence (24 wk)M 60 y, no worsening (4 wk) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Red scrotum</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mizes et al. (2021) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case report \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)M 64 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.25<span class="elsevierStyleHsp" style=""></span>mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gabapentin 300<span class="elsevierStyleHsp" style=""></span>mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CR (2 wk) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No recurrence (24 wk) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mehri et al. (2017) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case series (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2)M 56 yM 65 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.25<span class="elsevierStyleHsp" style=""></span>mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CR (4 wk) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No recurrence (24 wk) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Facial erythema and flushing associated with rosacea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Logger et al. (2020) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systematic review \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>18)17–59 y14 women4 men \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.125–6.25<span class="elsevierStyleHsp" style=""></span>mgbid or tid, adjusted up to 31.25<span class="elsevierStyleHsp" style=""></span>mg/d from 1 wk to 28 mo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Topical brimonidine 0.33% daily (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)Doxycycline or oral antihistamines/corticosteroids (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Significant improvement in erythema in less than 3 weeks in all casesReduction in cheek temperature (2.2–6.4°C) in all cases (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertigo and nausea (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)Sensation of weakness (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1)Hypotension (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not specified \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3325523.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Summary of Cases in the Literature Evaluating the Effectiveness of Carvedilol for Different Skin Conditions.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of beta-blockers for rosacea-associated facial erythema and flushing: a systematic review and update on proposed mode of action" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.G.M. Logger" 1 => "J.I. Olydam" 2 => "R.J.B. Driessen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2020.04.129" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2020" "volumen" => "83" "paginaInicial" => "1088" "paginaFinal" => "1097" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32360760" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel mechanism of carvedilol efficacy for rosacea treatment: toll-like receptor 2 inhibition in macrophages" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Zhang" 1 => "P. Jiang" 2 => "L. Sheng" 3 => "Y. Liu" 4 => "Y. Liu" 5 => "M. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fimmu.2021.609615" "Revista" => array:5 [ "tituloSerie" => "Front Immunol" "fecha" => "2021" "volumen" => "12" "paginaInicial" => "609615" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34322115" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined carvedilol and gabapentin treatment induces a rapid response in red scrotum syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Mizes" 1 => "O. Bunimovich" 2 => "Y.L. Bunimovich" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5070/D327553619" "Revista" => array:3 [ "tituloSerie" => "Dermatol Online J" "fecha" => "2021" "volumen" => "27" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Carvedilol for treatment of red vulva syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Hajj" 1 => "N. Ayoub" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamadermatol.2018.0246" "Revista" => array:6 [ "tituloSerie" => "JAMA Dermatol" "fecha" => "2018" "volumen" => "154" "paginaInicial" => "731" "paginaFinal" => "733" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29710286" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The β-blocker carvedilol prevented ultraviolet-mediated damage of murine epidermal cells and 3D human reconstructed skin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Chen" 1 => "S. Liang" 2 => "A. Shahid" 3 => "B.T. Andresen" 4 => "Y. Huang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/ijms21030798" "Revista" => array:5 [ "tituloSerie" => "Int J Mol Sci" "fecha" => "2020" "volumen" => "21" "paginaInicial" => "798" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31991834" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00017310/0000011400000010/v1_202311020433/S0001731023006968/v1_202311020433/en/main.assets" "Apartado" => array:4 [ "identificador" => "34907" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Foro de Residentes" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00017310/0000011400000010/v1_202311020433/S0001731023006968/v1_202311020433/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023006968?idApp=UINPBA000044" ]
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